PD-1 and TIGIT coexpression identifies a circulating CD8 T cell subset predictive of response to anti-PD-1 therapy

Autor: Valentin Voillet, Tiffany Beauvais, Brigitte Dréno, Charles Nardin, Régis Josien, Camille Dabrowski, Nathalie Labarrière, Stanley R. Riddell, Sylvain Simon, Candice D. Church, Nicolas Jouand, Raphael Gottardo, Olivier Adotevi, Amir Khammari, François Aubin, Steven P. Fling, Cécile Braudeau, Martin A. Cheever, Virginie Vignard, Paul Nghiem, Samuel Rulli, Nirasha Ramchurren, Caroline Laheurte, Zhong Wu
Přispěvatelé: Anti-Tumor Immunosurveillance and Immunotherapy (CRCINA-ÉQUIPE 3), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), LabEX IGO Immunothérapie Grand Ouest, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Centre hospitalier universitaire de Nantes (CHU Nantes), Qiagen Sciences [Frederick, MD, USA], Plateforme CYTOCELL Nantes (CRCINA-CYTOCELL), Clinical and Translational Research in Skin Cancer (CRCINA-ÉQUIPE 2), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Université de Nantes (UN)-Université de Nantes (UN), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de dermatologie (CHRU Besançon), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), SIRIC ILIAD (INCA-DGOS-Inserm_12558)BMS FoundationLigue contre le CancerRégion Pays de la Loire, ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Nantes Université (Nantes Univ), Département de dermatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), LABARRIERE, Nathalie, Laboratoires d'excellence - Immunothérapies Grand Ouest - - IGO2011 - ANR-11-LABX-0016 - LABX - VALID
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Cancer Research
medicine.medical_treatment
Programmed Cell Death 1 Receptor
CD8-Positive T-Lymphocytes
0302 clinical medicine
T-Lymphocyte Subsets
Immunotherapy Biomarkers
Immunology and Allergy
Cytotoxic T cell
Receptors
Immunologic
Immune Checkpoint Inhibitors
RC254-282
education.field_of_study
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
3. Good health
medicine.anatomical_structure
Oncology
[SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology
[SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology
030220 oncology & carcinogenesis
Molecular Medicine
immunotherapy
[SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy
Receptors
CXCR5
costimulatory and inhibitory T-Cell receptors
T cell
Immunology
Population
[SDV.CAN]Life Sciences [q-bio]/Cancer
Biology
03 medical and health sciences
Immune system
[SDV.CAN] Life Sciences [q-bio]/Cancer
TIGIT
Predictive Value of Tests
medicine
melanoma
Humans
education
Pharmacology
Immunotherapy
[SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy
Gene signature
Carcinoma
Merkel Cell
030104 developmental biology
Cancer research
CD8
Zdroj: Journal for Immunotherapy of Cancer
Journal for Immunotherapy of Cancer, BMJ Publishing Group 2020, 8, pp.e001631. ⟨10.1136/jitc-2020-001631⟩
Journal for Immunotherapy of Cancer, 2020, 8, pp.e001631. ⟨10.1136/jitc-2020-001631⟩
Journal for ImmunoTherapy of Cancer, Vol 8, Iss 2 (2020)
ISSN: 2051-1426
Popis: BackgroundClinical benefit from programmed cell death 1 receptor (PD-1) inhibitors relies on reinvigoration of endogenous antitumor immunity. Nonetheless, robust immunological markers, based on circulating immune cell subsets associated with therapeutic efficacy are yet to be validated.MethodsWe isolated peripheral blood mononuclear cell from three independent cohorts of melanoma and Merkel cell carcinoma patients treated with PD-1 inhibitor, at baseline and longitudinally after therapy. Using multiparameter flow cytometry and cell sorting, we isolated four subsets of CD8+ T cells, based on PD-1 and TIGIT expression profiles. We performed phenotypic characterization, T cell receptor sequencing, targeted transcriptomic analysis and antitumor reactivity assays to thoroughly characterize each of these subsets.ResultsWe documented that the frequency of circulating PD-1+TIGIT+ (DPOS) CD8+ T-cells after 1 month of anti-PD-1 therapy was associated with clinical response and overall survival. This DPOS T-cell population was enriched in highly activated T-cells, tumor-specific and emerging T-cell clonotypes and T lymphocytes overexpressing CXCR5, a key marker of the CD8 cytotoxic follicular T cell population. Additionally, transcriptomic profiling defined a specific gene signature for this population as well as the overexpression of specific pathways associated with the therapeutic response.ConclusionsOur results provide a convincing rationale for monitoring this PD-1+TIGIT+ circulating population as an early cellular-based marker of therapeutic response to anti-PD-1 therapy.
Databáze: OpenAIRE
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